ASCO GU 2022: Comparing Tumor Genomic Landscape Across Age, Disease Demographics

Posters from the American Society of Clinical Oncology Genitourinary Cancers Symposium (ASCO GU) 2022 examine how the tumor genomic landscape differs between patients with different types of urothelial carcinoma (UC) and younger and older patients with metastatic clear cell renal cell carcinoma (mccRCC).

Locally or Advanced UCS vs UC

Urothelial carcinoma with squamous differentiation (UCS) is a common genitourinary condition that is managed similarly to pure UC. Patients with locally advanced or metastatic UCS require focused study and there is limited data on the genomic profile of UCS. Investigators hypothesized that UCS has a distinct genomic landscape compared to pure UC.¹

The investigators conducted a retrospective study for patients with advanced UCS and UC who underwent tumor-based comprehensive genomic profiling (CGP). The cases were reviewed by a genitourinary pathologist and UCS diagnoses were based on the presence of any component of squamous differentiation. For inclusion in the analysis, gene alterations had to appear in at least 5% of patients.

Overall, 87 patients were included, 31 of whom had UCS and 56 had UC. The median age of the cohort was 66 years in the UCS group and 68 in the UC group. There were more men in the UCS group than the UC group. Alterations to KMT2D were significantly enriched in the UCS population compared with the UC group (n = 15/31 vs 0/56; P < .001). Also, gene alterations in CUL4A was found significantly more often in patients with UCS than those with UC (n = 4/31 vs 1/56; P = .03). The mutation burden of tumors and the frequency of genomic alterations in each patient were not significantly different between the groups.

The investigators concluded that identifying the underlying molecular targets and biomarkers of UCS and UC can help providers appropriate choose treatment regimens for their patients. The study had some limitations, including the small sample size and potential selection and confounding biases.

Age Differences Across mccRCC

RCC is more prominent among people aged 60 to 80 years old. However, younger patients are at a greater risk of having symptomatic tumors on presentation but with better pathological features and disease specific survival compared with senior patients. Investigators conducted a retrospective study to see whether the genomic landscape of patients with onset of RCC at a younger age significantly differed from that of patients with a disease onset at a later age.²

Patients with mccRCC and tumor CGP between the ages of 25 and 52 for the younger group (n = 54) and 68 to 77 for the older group (n = 38) were analyzed. Male patients accounted for the majority of both groups.

Alterations in VHL and LBRM1 were the most common gene alterations reported for the entire cohort. In the younger group, the most commonly reported alterations were in the TP53, BAP1, CDKN2B, and TSC1 genes. Alterations in the SETD2, TSC1, KDM5C, and TP53 genes were the most commonly reported for the older group.

The investigators said that tumor mutation burden and gene alteration frequency were similar between the cohorts. Additionally, there were no significant differences in the prevalence of actionable genomic alterations between the groups with mccRCC. Future research should investigate the epigenomic changes and transcriptomic profiling.

Reference

1. Tripathi N, Jo Y, Sayegh N, et al. Tumor genomic landscape of locally advanced or metastatic urothelial carcinoma with squamous differentiation (UCS) compared to pure urothelial carcinoma (UC). Presented at: ASCO GU 2022; February 17-19, 2022; San Francisco, CA. Abstract 553. doi:10.1200/JCO.2022.40.6_suppl.553
2. Tripathi N, Li H, Jo Y, et al. Tumor genomic landscape in younger compared to older patients (pts) with metastatic clear cell renal cell carcinoma (mccRCC). Presented at: ASCO GU 2022; February 17-19, 2022; San Francisco, CA. Abstract 373. doi:10.1200/JCO.2022.40.6_suppl.373